Behavior of poly(glycerol sebacate) plugs in chronic tympanic membrane perforations

Abstract

The tympanic membrane (TM), separating the external and middle ear, consists of fibrous connective tissue sandwiched between epithelial layers. To treat chronic ear infections, tympanostomy drainage tubes are placed in surgically created holes in TMs which can become chronic perforations upon extrusion. Perforations are repaired using a variety of techniques, but are limited by morbidity, unsatisfactory closure rates, or minimal regeneration of the connective tissue. A more effective, minimally-invasive therapy is necessary to enhance the perforation closure rate. Current research utilizing decellularized or alignate materials moderately enhance closure but the native TM architecture is not restored. Poly(glycerol sebacate) (PGS) is a biocompatible elastomer which supports cell migration and enzymatically degrades in contact with vascularized tissue. PGS spool-shaped plugs were manufactured using a novel process. Using minimally invasive procedures, these elastomeric plugs were inserted into chronic chinchilla TM perforations. As previously reported, effective perforation closure occurred as both flange surfaces were covered by confluent cell layers; >90% of perforations were closed at 6-week postimplantation. This unique in vivo environment has little vascularized tissue. Consequently, PGS degradation was minimal over 16-week implantation, hindering regeneration of the TM fibrous connective tissue. PGS degradation must be enhanced to promote complete TM regeneration.

Additive manufactured biodegradable poly(glycerol sebacate methacrylate) nerve guidance conduits

“…Sebacic acid copolymers have been FDA approved for use as drug delivery matrices [19], The use of PGS in tissue engineering has also been explored for cardiac patches [20,21], microfluidics [22], tympanic perforations [23], drug delivery [19], retinal transplantation [24] and neural repair [25]. PGS has previously been explored for its use as nerve guide material by Sundback et al [25].…”

Polyglycerol Hyperbranched Polyesters: Synthesis, Properties and Pharmaceutical and Biomedical Applications

“…When it comes to curing, increased curing duration resulted in more highly crosslinked polymers [102], with increased equilibrium Young's modulus [91], tangent modulus [103] and average ultimate tensile stress (UTS) [83,104] and a diminished strain at break (ε max ) [104]. The general idea is that increased curing time is synonym to increased stiffness [98,[105][106][107]. However, increasing curing time or temperature did not improve PGSeb properties indefinitely [98].…”

“…Several groups have used a silicon-based replica molding process to prepare PGSeb scaffolds: PGSeb prepolymer, molten or in solution, was cast on a silicon master with the appropriate features, the prepolymer was cured, and the final object delaminated from the silicon master ( Figure 6a). The use of a sacrificial layer (sucrose or maltose) between the silicon wafer and the prepolymer has proved to be beneficial when releasing the polymer from the wafer [105,[122][123][124].…”

“…PGSeb was found promising for the engineering of the temporomandibular joint disc [160] and the repair of chronic tympanic membrane (TM) perforations [105,161]. It was reported that 91% of TMs repaired with spool-shaped plugs of PGSeb had healed six weeks following implantation.…”

Bioactive Glass Fiber-Reinforced PGS Matrix Composites for Cartilage Regeneration

“…This elastomer is relatively inexpensive, exhibits thermoset elastomeric properties, and its in vivo degradation products can be eliminated through natural pathways [3]. PGS has been already applied in several studies with satisfying results regarding the regeneration of cardiac muscle [5,6,7], vascular tissue [8,9], cartilage [10,11], nerve conduits [12,13], retina [14,15], and tympanic membrane perforations [16,17]. …”